O60779 (S19A2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Thiamine transporter 1
Short name=ThTr-1
Short name=ThTr1

Alternative name(s):
Solute carrier family 19 member 2
Thiamine carrier 1
Short name=TC1

Gene names

Name:	SLC19A2
Synonyms:	THT1, TRMA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	497 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	High-affinity transporter for the intake of thiamine.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Ubiquitous; most abundant in skeletal and cardiac muscle. Medium expression in placenta, heart, liver and kidney, low in lung.
Involvement in disease	Thiamine-responsive megaloblastic anemia syndrome (TRMA) [MIM:249270]: An autosomal recessive disease characterized by megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Onset is typically between infancy and adolescence, but all of the cardinal findings are often not present initially. The anemia, and sometimes the diabetes, improves with high doses of thiamine. Other more variable features include optic atrophy, congenital heart defects, short stature, and stroke. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.10
Sequence similarities	Belongs to the reduced folate carrier (RFC) transporter (TC 2.A.48) family. [View classification]
Sequence caution	The sequence BAG64936.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Disease	Deafness Diabetes mellitus Disease mutation
Domain	Transmembrane Transmembrane helix
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	thiamine transmembrane transport Inferred from electronic annotation. Source: Compara thiamine transport Non-traceable author statement Ref.1. Source: UniProtKB thiamine-containing compound metabolic process Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Non-traceable author statement Ref.1. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome
Molecular_function	folic acid binding Inferred from electronic annotation. Source: InterPro folic acid transporter activity Non-traceable author statement Ref.1. Source: UniProtKB reduced folate carrier activity Inferred from electronic annotation. Source: InterPro thiamine uptake transmembrane transporter activity Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O60779-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O60779-2)

The sequence of this isoform differs from the canonical sequence as follows:
     69-269: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 497	497	Thiamine transporter 1		PRO_0000178663
Regions
	Topological domain	1 – 28	28	Cytoplasmic Potential
	Transmembrane	29 – 46	18	Helical; Potential
	Topological domain	47 – 72	26	Extracellular Potential
	Transmembrane	73 – 91	19	Helical; Potential
	Topological domain	92 – 99	8	Cytoplasmic Potential
	Transmembrane	100 – 118	19	Helical; Potential
	Topological domain	119 – 128	10	Extracellular Potential
	Transmembrane	129 – 149	21	Helical; Potential
	Topological domain	150 – 165	16	Cytoplasmic Potential
	Transmembrane	166 – 185	20	Helical; Potential
	Topological domain	186 – 191	6	Extracellular Potential
	Transmembrane	192 – 208	17	Helical; Potential
	Topological domain	209 – 285	77	Cytoplasmic Potential
	Transmembrane	286 – 310	25	Helical; Potential
	Topological domain	311 – 337	27	Extracellular Potential
	Transmembrane	338 – 354	17	Helical; Potential
	Topological domain	355 – 363	9	Cytoplasmic Potential
	Transmembrane	364 – 380	17	Helical; Potential
	Topological domain	381 – 386	6	Extracellular Potential
	Transmembrane	387 – 409	23	Helical; Potential
	Topological domain	410 – 419	10	Cytoplasmic Potential
	Transmembrane	420 – 443	24	Helical; Potential
	Topological domain	444 – 455	12	Extracellular Potential
	Transmembrane	456 – 479	24	Helical; Potential
	Topological domain	480 – 497	18	Cytoplasmic Potential
Amino acid modifications
	Glycosylation	63	1	N-linked (GlcNAc...) Potential
	Glycosylation	314	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	69 – 269	201	Missing in isoform 2.		VSP_036467
	Natural variant	93	1	D → H in TRMA. Ref.10		VAR_010249
	Natural variant	143	1	S → F in TRMA. Ref.10		VAR_010250
	Natural variant	172	1	G → D in TRMA. Ref.2 Corresponds to variant rs28937595 [ dbSNP | Ensembl ].		VAR_010248

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 24, 2001. Version 2. Checksum: 87A993E2B6FBFE96	FASTA	497	55,400
	10 20 30 40 50 60 MDVPGPVSRR AAAAAATVLL RTARVRRECW FLPTALLCAY GFFASLRPSE PFLTPYLLGP 70 80 90 100 110 120 DKNLTEREVF NEIYPVWTYS YLVLLFPVFL ATDYLRYKPV VLLQGLSLIV TWFMLLYAQG 130 140 150 160 170 180 LLAIQFLEFF YGIATATEIA YYSYIYSVVD LGMYQKVTSY CRSATLVGFT VGSVLGQILV 190 200 210 220 230 240 SVAGWSLFSL NVISLTCVSV AFAVAWFLPM PQKSLFFHHI PSTCQRVNGI KVQNGGIVTD 250 260 270 280 290 300 TPASNHLPGW EDIESKIPLN MEEPPVEEPE PKPDRLLVLK VLWNDFLMCY SSRPLLCWSV 310 320 330 340 350 360 WWALSTCGYF QVVNYTQGLW EKVMPSRYAA IYNGGVEAVS TLLGAVAVFA VGYIKISWST 370 380 390 400 410 420 WGEMTLSLFS LLIAAAVYIM DTVGNIWVCY ASYVVFRIIY MLLITIATFQ IAANLSMERY 430 440 450 460 470 480 ALVFGVNTFI ALALQTLLTL IVVDASGLGL EITTQFLIYA SYFALIAVVF LASGAVSVMK 490 KCRKLEDPQS SSQVTTS
	Isoform 2 [UniParc]. Checksum: A8C5CDFF6D54540C	FASTA	296	32,858
	10 20 30 40 50 60 MDVPGPVSRR AAAAAATVLL RTARVRRECW FLPTALLCAY GFFASLRPSE PFLTPYLLGP 70 80 90 100 110 120 DKNLTEREEP KPDRLLVLKV LWNDFLMCYS SRPLLCWSVW WALSTCGYFQ VVNYTQGLWE 130 140 150 160 170 180 KVMPSRYAAI YNGGVEAVST LLGAVAVFAV GYIKISWSTW GEMTLSLFSL LIAAAVYIMD 190 200 210 220 230 240 TVGNIWVCYA SYVVFRIIYM LLITIATFQI AANLSMERYA LVFGVNTFIA LALQTLLTLI 250 260 270 280 290 VVDASGLGLE ITTQFLIYAS YFALIAVVFL ASGAVSVMKK CRKLEDPQSS SQVTTS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the human thiamine transporter, a member of the folate transporter family." Dutta B., Huang W., Molero M., Kekuda R., Leibach F.H., Devoe L.D., Ganapathy V., Prasad P.D. J. Biol. Chem. 274:31925-31929(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta.
[2]	"Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness." Labay V., Raz T., Baron D., Mandel H., Williams H., Barrett T., Szargel R., McDonald L., Shalata A., Nosaka K., Gregory S., Cohen N. Nat. Genet. 22:300-304(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANT TRMA ASP-172.
[3]	"The gene mutated in thiamine-responsive anaemia with diabetes and deafness (TRMA) encodes a functional thiamine transporter." Fleming J.C., Tartaglini E., Steinkamp M.P., Schorderet D.F., Cohen N., Neufeld E.J. Nat. Genet. 22:305-308(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). Tissue: Skeletal muscle.
[4]	"Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive megaloblastic anaemia syndrome." Diaz G.A., Banikazemi M., Oishi K., Desnick R.J., Gelb B.D. Nat. Genet. 22:309-312(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fetal brain.
[5]	Subramanian V.S., Chatterjee N.S., Fleming J.C., Neufeld E.J., Said H.M. Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Colon.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon, Testis and Trachea.
[7]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Eye.
[10]	"The spectrum of mutations, including four novel ones, in the thiamine-responsive megaloblastic anemia gene SLC19A2 of eight families." Raz T., Labay V., Baron D., Szargel R., Anbinder Y., Barrett T., Rabl W., Viana M.B., Mandel H., Baruchel A., Cayuela J.-M., Cohen N. Hum. Mutat. 16:37-42(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TRMA HIS-93 AND PHE-143.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF160812 mRNA. Translation: AAF15129.1. AJ238413 Genomic DNA. Translation: CAB50771.1. AJ237724 mRNA. Translation: CAB50770.1. AF135488 mRNA. Translation: AAD45985.1. AF158233 Genomic DNA. Translation: AAD51280.1. Sequence problems. AF160186 Genomic DNA. Translation: AAD51283.1. Sequence problems. AF160756 Genomic DNA. Translation: AAD54242.1. AF153330 mRNA. Translation: AAD43534.1. AF272359 mRNA. Translation: AAK54468.1. AK304021 mRNA. Translation: BAG64936.1. Different initiation. AK313779 mRNA. Translation: BAG36517.1. AK316465 mRNA. Translation: BAH14836.1. AL021068 Genomic DNA. Translation: CAI19780.1. AL021068 Genomic DNA. Translation: CAI19782.1. CH471067 Genomic DNA. Translation: EAW90843.1. CH471067 Genomic DNA. Translation: EAW90846.1. BC018514 mRNA. Translation: AAH18514.1.
IPI	IPI00031631. IPI00103058.
RefSeq	NP_008927.1. NM_006996.2.
UniGene	Hs.30246.
3D structure databases
ProteinModelPortal	O60779.
ModBase	Search...
Protein-protein interaction databases
IntAct	O60779. 1 interaction.
STRING	9606.ENSP00000236137.
Protein family/group databases
TCDB	2.A.48.2.1. reduced folate carrier (RFC) family.
PTM databases
PhosphoSite	O60779.
Proteomic databases
PaxDb	O60779.
PRIDE	O60779.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000236137; ENSP00000236137; ENSG00000117479. ENST00000367804; ENSP00000356778; ENSG00000117479.
GeneID	10560.
KEGG	hsa:10560.
UCSC	uc001gge.4. human. uc001ggf.4. human.
Organism-specific databases
CTD	10560.
GeneCards	GC01M169433.
HGNC	HGNC:10938. SLC19A2.
HPA	HPA006119. HPA016599.
MIM	249270. phenotype. 603941. gene.
neXtProt	NX_O60779.
Orphanet	49827. Thiamine-responsive megaloblastic anemia syndrome.
PharmGKB	PA35825.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG241030.
HOVERGEN	HBG054198.
InParanoid	O60779.
KO	K14610.
OMA	NGAVSIM.
OrthoDB	EOG4DNF4P.
PhylomeDB	O60779.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
SABIO-RK	O60779.
Gene expression databases
ArrayExpress	O60779.
Bgee	O60779.
CleanEx	HS_SLC19A2.
Genevestigator	O60779.
GermOnline	ENSG00000117479. Homo sapiens.
Family and domain databases
InterPro	IPR002666. Folate_carrier. IPR016196. MFS_dom_general_subst_transpt. [Graphical view]
PANTHER	PTHR10686. PTHR10686. 1 hit.
Pfam	PF01770. Folate_carrier. 1 hit. [Graphical view]
PIRSF	PIRSF028739. Folate_carrier. 1 hit.
SUPFAM	SSF103473. MFS_gen_substrate_transporter. 1 hit.
ProtoNet	Search...
Other
BindingDB	O60779.
ChEMBL	CHEMBL3079.
ChiTaRS	SLC19A2. human.
GenomeRNAi	10560.
NextBio	40077.
SOURCE	Search...

Entry information

Entry name

S19A2_HUMAN

Accession

Primary (citable) accession number: O60779
Secondary accession number(s): B2R9H0 , B4E1X4, Q8WV87, Q9UBL7, Q9UKJ2, Q9UN31, Q9UN43

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 24, 2001
Last modified:	May 1, 2013
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.